Dopaminergic cell death in the substantia nigra SN is central toParkinson’s disease PD, but the neurodegenerative mechanismshave not been completely elucidated. Iron accumulation in dopaminergicand glial cells in the SN of PD patients may contribute tothe generation of oxidative stress, protein aggregation, and neuronaldeath. The mechanisms involved in iron accumulation alsoremain unclear. Here, we describe an increase in the expression ofan isoform of the divalent metal transporter 1 DMT1-Nramp2-Slc11a2 in the SN of PD patients. Using the PD animal model of1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP intoxicationin mice, we showed that DMT1 expression increases in the ventralmesencephalon of intoxicated animals, concomitant with ironaccumulation, oxidative stress, and dopaminergic cell loss. In addition,we report that a mutation in DMT1 that impairs irontransport protects rodents against parkinsonism-inducing neurotoxinsMPTP and 6-hydroxydopamine. This study supports a